Water → tert-butyl N-(3-hydroxy-3-methylcyclobutyl)carbamate

HRID 577723Notes

Reaction equation

HRID 577723 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][C:10]2([O:12][CH2:11]2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([BH-](CC)CC)C.[Li+].O.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][C:10]([OH:12])([CH3:11])[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 23664628LithiumtriethylborohydrideHCID 585207851154759-69-9

Product 1

HCID 72207356tert-butyl N-(3-hydroxy-3-methylcyclobutyl)carbamateYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

(1-Oxa-spiro[2.3]hex-5-yl)-carbamic acid tert-butyl ester (˜1:1 cis/trans mixture, 3.93 g, 19.7 mmol) was dissolved in anhydrous THF (100 mL) and cooled to 0° C. in an ice/water bath. To this was added a 1.0 M solution of lithium triethylborohydride in THF (25 mL) via dropping addition funnel, over 10 min, then the mixture stirred at 0° C. for 3.5 hours. While still cooled to 0° C., 30 mL deionized water was added dropwise over 5 minutes to quench the reaction. After warming to rt, solid potassium carbonate was added to saturate the aqueous phase, allowing the layers to be separated. The aqueous layer was further extracted with ethyl acetate (2×30 mL). The combined organic layers (THF and EtOAc) were dried over magnesium sulfate, filtered, concentrated, and purified by silica gel chromatography (eluting with 40-80% ethyl acetate in heptanes), affording the title compound (3.16 g, 80%) as a white solid. NMR shows a 55:45 ratio of N,O-cis/trans isomers. 1H NMR (400 MHz, chloroform-d) δ ppm [1.37 (s) and 1.41 (s), 3H together] 1.44 (s, 9H) 1.66 (br. s., 1H) 1.89-2.03 (m, 2H) 2.42-2.54 (m, 2H)

Workup

  1. additionaddition funnel
  2. temperatureWhile still cooled to 0° C.
  3. additionwas added dropwise over 5 minutes
  4. customto quench
  5. customthe reaction
  6. temperatureAfter warming to rt
  7. concentrationto saturate the aqueous phase
  8. customto be separated
  9. extractionThe aqueous layer was further extracted with ethyl acetate (2×30 mL)
  10. dry with materialThe combined organic layers (THF and EtOAc) were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurified by silica gel chromatography (eluting with 40-80% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-9662147676074295a049cf8e435548dd
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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